Surface plasmon resonance microscopy reveals N-glycosylation driven modulation of affinity and avidity of ErbB receptors in whole single pancreatic cancer cells.
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| Titel: | Surface plasmon resonance microscopy reveals N-glycosylation driven modulation of affinity and avidity of ErbB receptors in whole single pancreatic cancer cells. |
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| Autoren: | Aguilar Díaz de León JS; Biosensing Instrument Inc., 1007 E. Warner Rd, Tempe, Az, 85284, United States., Thirumurthy M; Biosensing Instrument Inc., 1007 E. Warner Rd, Tempe, Az, 85284, United States., Ly N; Biosensing Instrument Inc., 1007 E. Warner Rd, Tempe, Az, 85284, United States. |
| Quelle: | Glycobiology [Glycobiology] 2025 Nov 29; Vol. 35 (12). |
| Publikationsart: | Journal Article |
| Sprache: | English |
| Info zur Zeitschrift: | Publisher: IRL Press at Oxford University Press Country of Publication: England NLM ID: 9104124 Publication Model: Print Cited Medium: Internet ISSN: 1460-2423 (Electronic) Linking ISSN: 09596658 NLM ISO Abbreviation: Glycobiology Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Oxford ; New York : IRL Press at Oxford University Press, c1990- |
| MeSH-Schlagworte: | Pancreatic Neoplasms*/metabolism , Pancreatic Neoplasms*/pathology , ErbB Receptors*/metabolism , ErbB Receptors*/immunology , Receptor, ErbB-2*/metabolism , Receptor, ErbB-3*/metabolism, Humans ; Glycosylation ; Surface Plasmon Resonance ; Cell Line, Tumor ; Trastuzumab |
| Abstract: | Glycans found on the ErbB family of receptors (HER1, HER2, and HER3) represent promising targets for cancer treatment. Characterization and full quantification of the bivalent kinetic interactions of therapeutic antibodies against the ErbB family of receptors directly in their native cancer cellular environment represent a unique strategy to help overcome cancer drug resistance and to the development of more effective therapeutic drugs. In this study, surface plasmon resonance microscopy (SPRM) was implemented in a unique and innovative manner to quantify the bivalent kinetic interactions of monoclonal antibodies targeting HER1 (EFGR), HER2 and HER3 directly on whole BXPC3 pancreatic cancer cells under a glycosylated (native) and deglycosylated cellular environment. Results revealed in unprecedented detail that both the single-arm affinity and double-arm stronger avidity modes of binding interaction could be observed. For bivalent Cetuximab (anti-HER1) KDs of 151 nM and 4.6 nM were observed, for bivalent Herceptin (anti-HER2) KDs of 2 nM and 0.1 nM were observed, and for bivalent anti-HER3 KDs of 13 nM and 1.3 nM were observed. However, upon enzymatic N-deglycosylation of BXPC3 cells, HER1 and HER3 demonstrated significant increase in affinity of 1000-fold and 21-fold, respectively. In contrast, HER2 kinetic interactions were negligibly influenced by cellular N-deglycosylation of BXPC3 cells. This study highlights for the first time SPRM's unique ability to characterize the bivalent heterogeneous kinetic interactions of monoclonal antibodies with ErbB receptors on whole cancer cells, and to quantify the shielding influence of pancreatic cancer cell surface N-glycosylation on these interactions. (© The Author(s) 2025. Published by Oxford University Press.) |
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| Grant Information: | R42 GM143986 United States GM NIGMS NIH HHS; R42 GM154550 United States GM NIGMS NIH HHS; R42GM154550 National Institute of Health; R42GM143986 National Institute of Health |
| Contributed Indexing: | Keywords: affinity/avidity/ErbB receptors/ /N-glycosylation/surface plasmon resonance microscopy (SPRM) |
| Substance Nomenclature: | EC 2.7.10.1 (ErbB Receptors) EC 2.7.10.1 (Receptor, ErbB-2) EC 2.7.10.1 (Receptor, ErbB-3) EC 2.7.10.1 (EGFR protein, human) EC 2.7.10.1 (ERBB2 protein, human) EC 2.7.10.1 (ERBB3 protein, human) P188ANX8CK (Trastuzumab) |
| Entry Date(s): | Date Created: 20251018 Date Completed: 20251201 Latest Revision: 20251204 |
| Update Code: | 20251204 |
| PubMed Central ID: | PMC12665891 |
| DOI: | 10.1093/glycob/cwaf066 |
| PMID: | 41108118 |
| Datenbank: | MEDLINE |
Nájsť tento článok vo Web of Science | Abstract: | Glycans found on the ErbB family of receptors (HER1, HER2, and HER3) represent promising targets for cancer treatment. Characterization and full quantification of the bivalent kinetic interactions of therapeutic antibodies against the ErbB family of receptors directly in their native cancer cellular environment represent a unique strategy to help overcome cancer drug resistance and to the development of more effective therapeutic drugs. In this study, surface plasmon resonance microscopy (SPRM) was implemented in a unique and innovative manner to quantify the bivalent kinetic interactions of monoclonal antibodies targeting HER1 (EFGR), HER2 and HER3 directly on whole BXPC3 pancreatic cancer cells under a glycosylated (native) and deglycosylated cellular environment. Results revealed in unprecedented detail that both the single-arm affinity and double-arm stronger avidity modes of binding interaction could be observed. For bivalent Cetuximab (anti-HER1) KDs of 151 nM and 4.6 nM were observed, for bivalent Herceptin (anti-HER2) KDs of 2 nM and 0.1 nM were observed, and for bivalent anti-HER3 KDs of 13 nM and 1.3 nM were observed. However, upon enzymatic N-deglycosylation of BXPC3 cells, HER1 and HER3 demonstrated significant increase in affinity of 1000-fold and 21-fold, respectively. In contrast, HER2 kinetic interactions were negligibly influenced by cellular N-deglycosylation of BXPC3 cells. This study highlights for the first time SPRM's unique ability to characterize the bivalent heterogeneous kinetic interactions of monoclonal antibodies with ErbB receptors on whole cancer cells, and to quantify the shielding influence of pancreatic cancer cell surface N-glycosylation on these interactions.<br /> (© The Author(s) 2025. Published by Oxford University Press.) |
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| ISSN: | 1460-2423 |
| DOI: | 10.1093/glycob/cwaf066 |